I don't think I'd recommend two first time visitors walking with luggage from 125th and St. Nick to 120th and Lenox (Malcolm X) at 11pm.

No matter how you walk it (and it's about 1km depending on which route you take) you're going to have to walk on blocks that have few if any businesses open at night, and I consider blocks lined with open businesses to be a good indicator of safety in an unfamiliar neighborhood, since I can always duck into a shop if I feel unsafe for any reason.

If the extra expense isn't too big a deal, I think taking a cab from a busier part of town (Penn Station, Columbus Circle, the Lexington stop on the E train, or even all the way from the airport) is a better idea. You'll still get to see the streetscape, but won't have to experience it for the first time on foot with luggage in tow.